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Alveolar-Like Macrophages Can Limit Respiratory Syncytial Virus Infection in Mice
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A2860 - Alveolar-Like Macrophages Can Limit Respiratory Syncytial Virus Infection in Mice
Author Block: T. J. Moraes, S. Cen, M. L. Litvack, M. Post; The Hospital for Sick Children, Toronto, ON, Canada.
Background/rationale: Respiratory syncytial virus (RSV) is a common and significant pathogen in need of a therapy. Macrophages are known to play an important role in vivo protecting the host from RSV infection. Our group has generated alveolar-like macrophages (ALMs) from stem cells and we have data that these ALMs reduce RSV infection in cell culture. Here we tested the potential for ALMs to reduce RSV infection in vivo.
Methods: We utilized a mouse model of RSV infection. Briefly, 6 to 8 week old female Balb/C mice were sedated with isoflurane and 5 x 10e6 PFU RSV-A2 was instilled intranasally. Mice were monitored daily and then sacrificed on day 4 whereupon lungs were harvested for histological analysis and viral titres determined by plaque assay. Two days prior to RSV infection, mice received 1 x 10e6 ALMs by intra-tracheal installation. Control mice received a similar number of fibroblasts or no cells.
Results: Mice that received ALMs before RSV infection showed less weight loss when compared to infected control mice (fibroblast or no cell controls). Viral titers were significantly reduced in the ALM group. Finally, histological analysis demonstrated less evidence of inflammation and injury in the ALM prophylaxed mice.
Conclusions: Our findings suggest that ALMs can reduce RSV titers and RSV associated pathology in mice when the ALMs are delivered prior to RSV. Future experiments will focus on characterizing the mechanism behind the anti-RSV effect and on examining the efficacy of ALMs delivered post RSV infection.
Author Block: T. J. Moraes, S. Cen, M. L. Litvack, M. Post; The Hospital for Sick Children, Toronto, ON, Canada.
Background/rationale: Respiratory syncytial virus (RSV) is a common and significant pathogen in need of a therapy. Macrophages are known to play an important role in vivo protecting the host from RSV infection. Our group has generated alveolar-like macrophages (ALMs) from stem cells and we have data that these ALMs reduce RSV infection in cell culture. Here we tested the potential for ALMs to reduce RSV infection in vivo.
Methods: We utilized a mouse model of RSV infection. Briefly, 6 to 8 week old female Balb/C mice were sedated with isoflurane and 5 x 10e6 PFU RSV-A2 was instilled intranasally. Mice were monitored daily and then sacrificed on day 4 whereupon lungs were harvested for histological analysis and viral titres determined by plaque assay. Two days prior to RSV infection, mice received 1 x 10e6 ALMs by intra-tracheal installation. Control mice received a similar number of fibroblasts or no cells.
Results: Mice that received ALMs before RSV infection showed less weight loss when compared to infected control mice (fibroblast or no cell controls). Viral titers were significantly reduced in the ALM group. Finally, histological analysis demonstrated less evidence of inflammation and injury in the ALM prophylaxed mice.
Conclusions: Our findings suggest that ALMs can reduce RSV titers and RSV associated pathology in mice when the ALMs are delivered prior to RSV. Future experiments will focus on characterizing the mechanism behind the anti-RSV effect and on examining the efficacy of ALMs delivered post RSV infection.
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